Lysosomal enzymes are secreted by many cell types into the extracellular environment where they are thought to produce tissue damage. Two cell types which are actively secreting lysosomal hydrolases are the polymorphonuclear leukocyte and the mononuclear phagocyte. Moreover, the pulmonary macrophage appears to be a pivotal cell in regulating turnover of macromolecules in the lung as well as providing defense against invading pathogens. Recently it has been observed that cells in vivo and in vitro have the capability to take up hydrolases by receptor-mediated pinocytosis. The mononuclear phagocyte has the ability to take up hydrolases by two mutually exclusive cell surface receptors which recognize mannose-6-phosphate and mannose, respectively, when they appear as terminal sugars on the oligosaccharide chains of the hydrolase. The expression of these two receptors by mononuclear phagocytes appears to be closely modulated. The experiments outlined in this proposal are designed to gain some understanding of the mechanisms of receptor regulation in mononuclear phagocytes and their role in the uptake of lysosomal hydrolases.